Regulation Of Peripheral Vascular Resistance Research Articles

Study of blood vessels reaction to local heating by imaging photoplethysmography

The possibility of using a new contactless method of imaging photoplethysmography to assess thermoregulatory vasodilatation of blood vessels was studied. Perfusion reaction in a region of the outer forearm in response to local heating up to 41 ± 1 °C was monitored in six volunteers aged 39–52 years using a video recording of the study area, synchronized with an electrocardiogram, and subsequent correlation processing of the data obtained. It was shown that the change in perfusion during local heating has a biphasic type and is due to the response of the nervous system mediated by the axon reflex in the first phase of vasodilation and the synthesis of nitric oxide in endothelial cells in the second phase of vasodilation. It was revealed that the multiple increase in perfusion in the first phase of heating depends both on the initial temperature of the skin and on the difference in its heating temperature. It was found that for a significant development of a vascular response to hyperthermia associated with the activation of endothelial function, heating of tissues for more than 15 minutes is necessary. It was shown that the method of imaging photoplethysmography reliably reflects the work of the mechanisms of regulation of peripheral vascular resistance which is of great prognostic value for the detection of primary signs of cardiovascular diseases.

Probenecid Inhibits α-Adrenergic Receptor-Mediated Vasoconstriction in the Human Leg Vasculature.

Coordination of vascular smooth muscle cell tone in resistance arteries plays an essential role in the regulation of peripheral resistance and overall blood pressure. Recent observations in animals have provided evidence for a coupling between adrenoceptors and Panx1 (pannexin-1) channels in the regulation of sympathetic nervous control of peripheral vascular resistance and blood pressure; however, evidence for a functional coupling in humans is lacking. We determined Panx1 expression and effects of treatment with the pharmacological Panx1 channel inhibitor probenecid on the vasoconstrictor response to α1- and α2-adrenergic receptor stimulation in the human forearm and leg vasculature of young healthy male subjects (23±3 years). By use of immunolabeling and confocal microscopy, Panx1 channels were found to be expressed in vascular smooth muscle cells of arterioles in human leg skeletal muscle. Probenecid treatment increased (P<0.05) leg vascular conductance at baseline by ≈15% and attenuated (P<0.05) the leg vasoconstrictor response to arterial infusion of tyramine (α1- and α2-adrenergic receptor stimulation) by ≈15%, whereas the response to the α1-agonist phenylephrine was unchanged. Inhibition of α1-adrenoceptors prevented the probenecid-induced increase in baseline leg vascular conductance, but did not alter the effect of probenecid on the vascular response to tyramine. No differences with probenecid treatment were detected in the forearm. These observations provide the first line of evidence in humans for a functional role of Panx1 channels in setting resting tone via α1-adrenoceptors and in the constrictive effect of noradrenaline via α2-adrenoceptors, thereby contributing to the regulation of peripheral vascular resistance and blood pressure in humans.

Endogenous Digitalis-Like Factors: An Overview of the History

The sodium pump is a ubiquitous cell surface enzyme, a Na, K ATPase, which maintains ion gradients between cells and the extracellular fluid (ECF). The extracellular domain of this enzyme contains a highly conserved binding site, a receptor for a plant derived family of compounds, the digitalis glycosides. These compounds inhibit the enzyme and are used in the treatment of congestive heart failure and certain cardiac arrhythmias. The highly conserved nature of this enzyme and its digitalis receptor led to early suggestions that endogenous regulators might exist. Recent examination of this hypothesis emerged from research in two separate areas: the regulation of ECF volume by a natriuretic hormone (NH), and the regulation of peripheral vascular resistance by a circulating inhibitor of vascular Na, K ATPase. These two areas merged with the hypothesis that NH and the vascular Na, K ATPase inhibitor were in fact the same entity, and that it played a causative role in the pathophysiology of certain types of hypertension. The possibility that multiple endogenous digitalis-like factors (EDLFs) exist emerged from efforts to characterize the circulating enzyme inhibitory activity. In this review, the development of this field from its beginnings is traced, the current status of the structure of EDLFs is briefly discussed, and areas for future development are suggested.

Increased vascular smooth muscle cell stiffness: a novel mechanism for aortic stiffness in hypertension

Increased vascular stiffness is fundamental to hypertension, and its complications, including atherosclerosis, suggest that therapy should also be directed at vascular stiffness, rather than just the regulation of peripheral vascular resistance. It is currently held that the underlying mechanisms of vascular stiffness in hypertension only involve the extracellular matrix and endothelium. We hypothesized that increased large-artery stiffness in hypertension is partly due to intrinsic mechanical properties of vascular smooth muscle cells. After confirming increased arterial pressure and aortic stiffness in spontaneously hypertensive rats, we found increased elastic stiffness of aortic smooth muscle cells of spontaneously hypertensive rats compared with Wistar-Kyoto normotensive controls using both an engineered aortic tissue model and atomic force microscopy nanoindentation. Additionally, we observed different temporal oscillations in the stiffness of vascular smooth muscle cells derived from hypertensive and control rats, suggesting that a dynamic component to cellular elastic stiffness is altered in hypertension. Treatment with inhibitors of vascular smooth muscle cell cytoskeletal proteins reduced vascular smooth muscle cell stiffness from hypertensive and control rats, suggesting their participation in the mechanism. This is the first study demonstrating that stiffness of individual vascular smooth muscle cells mediates vascular stiffness in hypertension, a novel concept, which may elucidate new therapies for hypertension and for vascular stiffness.

Nonlinear cardiovascular regulation consequent to changes in blood viscosity

Increasing blood and plasma viscosity is generally associated with pathological conditions, and increased cardiovascular risk, a perception based in part on studies where blood viscosity is increased to extreme values attained by hemoconcentration. Present studies, supported by epidemiological studies in humans, show that moderate increases in Hct improve cardiovascular function and vice versa. This result is due to the nonlinear regulation of peripheral vascular resistance arising from the increased production of nitric oxide following the increase of shear stress on the vascular wall due to increasing blood viscosity. Similar effects are found in when plasma viscosity is increased in the extremely hemodiluted circulation. In both cases there is an effect at the arteriolar/capillary level, leading to a condition of improved microvascular function and supra perfusion that facilitates clearance of metabolic waste products, while maintaining oxygen delivery. Application of these findings to the design of viscogenic plasma expanders suggests a new approach for the treatment of hemorrhage that in part replaces the use of blood transfusions, making it feasible to lower the transfusion trigger to levels below than normally considered safe.

Regulation of Maternal and Fetal Hemodynamics by Heme Oxygenase in Mice1

Heme oxygenase (HMOX) regulates vascular tone and blood pressure through the production of carbon monoxide (CO), a vasodilator derived from the heme degradation pathway. During pregnancy, the maternal circulation undergoes significant adaptations to accommodate the hemodynamic demands of the developing fetus. Our objective was to investigate the role of HMOX on maternal and fetal hemodynamics during pregnancy in a mouse model. We measured and compared maternal tissue and placental HMOX activity and endogenous CO production, represented by excreted CO and carboxyhemoglobin levels, during pregnancy (Embryonic Days 12.5-15.5) to nonpregnant controls. Micro-ultrasound was used to monitor maternal abdominal aorta diameters as well as blood flow velocities and diameters of fetal umbilical arteries. Tin mesoporphyrin, a potent HMOX inhibitor, was used to inhibit HMOX activity. Changes in maternal vascular tone were monitored by tail cuff blood pressure measurements. Effects of HMOX inhibition on placental structures were assessed by histology. We showed that maternal tissue and placental HMOX activity and CO production were significantly elevated during pregnancy. When HMOX in the placenta was inhibited, maternal and fetal hemodynamics underwent significant changes, with maternal blood pressures increasing. We concluded that increases in maternal tissue and placental HMOX activity contribute to the regulation of peripheral vascular resistance and therefore are important for the maintenance of normal maternal vascular tone and fetal hemodynamic functions during pregnancy.

Sensory Neurons With Afferents From Hind Limbs

Sensory nerve fibers from the dorsal root ganglia (DRG) may contribute to the regulation of peripheral vascular resistance. Axons of DRG neurons of the lower thoracic cord project mainly to resistance vessels in the lower limbs, likely opposing the vasoconstrictor effects of the sympathetic activity. This mechanism might be of importance in hypertension with increased sympathetic activity. We tested the hypothesis that sensory neurons of the DRG in the lower thoracic cord show an altered sensitivity to mechanical stimuli in hypertension. Neurons from DRG (T11 to L1) of rats with hypertension (2 kidney-1 clip hypertensive rats and 5 of 6 nephrectomized rats) were cultured on coverslips. Current time relationships were established with whole-cell patch recordings. Cells were characterized under control conditions and after exposure to hypoosmotic solutions to induce mechanical stress. Neurons with projections to the kidney were studied for comparison. The hypoosmotic extracellular medium induced a significant change in conductance of the cells in all of the groups of rats. In hypertensive rats, responses of cells with hindlimb axons were significantly different from controls: (2 kidney-1 clip hypertensives: delta-351+/-52 pA and 5 of 6 nephrectomized rats: delta-372+/-43 pA versus controls: delta-190+/-25 pA; P<0.05). Responses of DRG cells with renal afferents to mechanical stress were unaffected. Neurons from DRG in the lower thoracic cord with projections to the lower limbs exhibited an increased sensitivity to mechanical stress. We speculate that this observation may indicate an increased activity of these neurons, their axons, and neurotransmitters in the control of resistance vessels in hypertension.

Type 2 Diabetic Mice Have Increased Arteriolar Tone and Blood Pressure

Type 2 diabetes mellitus (T2-DM) is frequently associated with vascular dysfunction and elevated blood pressure, yet the underlying mechanisms are not completely understood. We hypothesized that in T2-DM, the regulation of peripheral vascular resistance is altered because of changes in local vasomotor mechanisms. In mice with T2-DM (C57BL/KsJ-(db-)/db-), systolic and mean arterial pressures measured by the tail cuff method were significantly elevated compared with those of control (db+/db-) animals (db/db, 146+/-5 and 106+/-2 mm Hg versus control, 133+/-4 and 98+/-4 mm Hg, respectively; P<0.05). Total peripheral resistance, calculated from cardiac output values (measured by echocardiography) and mean arterial pressure were significantly elevated in db/db mice (db/db, 25+/-6 versus control, 15+/-1 mm Hg[middot]mL(-1)[middot]min(-1)). In isolated, pressurized gracilis muscle arterioles (diameter approximately 80 microm) from db/db mice, stepwise increases in intraluminal pressure (from 20 to 120 mm Hg) elicited a greater reduction in diameter than in control vessels at each pressure step (at 80 mm Hg, db/db, 66+/-4% versus control, 79+/-3%). The passive diameters of arterioles (obtained in Ca2+-free solution) and the calculated myogenic index were not significantly different in the 2 groups. The presence of the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 did not affect arteriolar diameters of control mice but reduced the enhanced arteriolar tone of db/db mice back to control levels (at 80 mm Hg, 80+/-4%). The inhibitor of cyclooxygenase-1 (COX-1), SC-560, did not affect the basal tone of arterioles, whereas NS-398, an inhibitor of COX-2, caused a significant shift in the arteriolar pressure-diameter curve of vessels from db/db mice (at 80 mm Hg, 76+/-3%) but not in those of control mice. Also, in aortas of db/db mice, expression of COX-2 was enhanced compared with controls. Collectively, these findings suggest that in mice with T2-DM, the basal tone of skeletal muscle arterioles is increased because of an enhanced COX-2-dependent production of constrictor prostaglandins. These alterations in microvascular prostaglandin synthesis may contribute to the increase in peripheral resistance and blood pressure in T2-DM.

Endogenous digitalis-like factors. an historical overview

The sodium pump is a ubiquitous cell surface enzyme, a Na/K-ATPase, that maintains ion gradients between cells and the extracellular fluid. The extracellular domain of this enzyme contains a highly conserved receptor for a plant-derived family of compounds, the digitalis glycosides, used in the treatment of congestive heart failure, and certain cardiac arrhythmias. The concept that an endogenous modulator of this enzyme, analogous to the cardiac glycosides, emerged from work on two separate areas: the regulation of extracellular fluid (ECF) volume by a natriuretic hormone (NH), and the regulation of peripheral vascular resistance by a circulating inhibitor of vascular Na/K-ATPase. These two areas merged with the hypothesis that natriuretic hormone and the vascular Na/K-ATPase inhibitor were the same factor, and furthermore, that this factor played a causative role in the pathophysiology of certain types of hypertension. In this communication, the development of this field from its beginnings is traced; evidence for the existence of and efforts to identify the structure of this factor are briefly reviewed, and suggestions for future development of the field are put forward.

Evidence for a functional calcium-sensing receptor that modulates myogenic tone in rat subcutaneous small arteries

Myogenic tone of small arteries is dependent on the presence of extracellular calcium (Ca(o)(2+)), and, recently, a receptor that senses changes in Ca(2+), the calcium-sensing receptor (CaR), has been detected in vascular tissue. We investigated whether the CaR is involved in the regulation of myogenic tone in rat subcutaneous small arteries. Immunoblot analysis using a monoclonal antibody against the CaR demonstrated its presence in rat subcutaneous arteries. To determine whether the CaR was functionally active, segments of artery (< 250 microm internal diameter) mounted in a pressure myograph with an intraluminal pressure of 70 mmHg were studied after the development of myogenic tone. Increasing Ca(o)(2+) concentration ([Ca(2+)](o)) cumulatively from 0.5 to 10 mM induced an initial constriction (0.5-2 mM) followed by dilation (42 +/- 5% loss of tone). The dose-dependent dilation was mimicked by other known CaR agonists including magnesium (1-10 mM) and the aminoglycosides neomycin (0.003-10 mM) and kanamycin (0.003-3 mM). PKC activation with the phorbol ester phorbol-12,13-dibutyrate (20nM) inhibited the dilation induced by high [Ca(2+)](o) or neomycin, whereas inhibition of PKC with GF109203X (10 microM) increased the responses to Ca(o)(2+) or neomycin, consistent with the role of PKC as a negative regulator of the CaR. We conclude that rat subcutaneous arteries express a functionally active CaR that may be involved in the modulation of myogenic tone and hence the regulation of peripheral vascular resistance.

Vasoactivity of diadenosine polyphosphates in human small renal resistance arteries.

We examined for the first time the vascular effects of purinergic agents that contribute to the regulation of peripheral vascular resistance in human small renal resistance arteries (hRRAs). Diadenosine polyphosphates (ApnAs, n = 3-6) and ATP, mounted in a microvessel myograph, caused vasoconstriction in hRRAs (rank order of potency: Ap5A > Ap6A = Ap4A > Ap3A = ATP). ADP, AMP and adenosine had less contractile potency than ApnA, suggesting that the observed effects were not induced by ApnA degradation products. The ApnA agent, Ap5A, but not Ap4A, induced vasoconstrictions that were inhibited by pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; a P2X purinoceptor antagonist), but not by ADP3'5' (a P2Y purinoceptor antagonist). In pre-contracted hRRAs, all of the ApnA agents caused vasorelaxation, and the potencies did not differ from each other. The ApnA degradation products had less vasorelaxing potencies than ApnA, suggesting that the vasorelaxation was caused by the ApnA agents themselves. Ap4A-induced vasorelaxation was inhibited by ADP3'5' and PPADS. In contrast, Ap5A-induced vasorelaxation was not antagonized by ADP3'5', but was antagonized more strongly by PPADS than was Ap4A. We found that the tone of resistance arteries in human kidneys can be considerably influenced by these purinergic agonists, and most potently by ApnAs. Ap5A-induced vasoconstriction appeared to be mediated by P2X purinoceptors, whereas constriction due to Ap4A was caused by a different purinoceptor. Vasorelaxation due to Ap4A, but not Ap5A, appeared to be mediated by P2Y purinoceptors.

Differential effects of carvedilol and metoprolol on sympathetic regulation of peripheral vascular resistance in patients with chronic heart failure

Differential effects of carvedilol and metoprolol on sympathetic regulation of peripheral vascular resistance in patients with chronic heart failure

Mechanisms of heart rate and arterial blood pressure control: implications for the pathophysiology of neurocardiogenic syncope.

Neurocardiogenic syncope is a general term that describes syncope resulting from altered autonomic activity, as manifested by abnormal regulation of peripheral vascular resistance and heart rate. Although there has been great interest in the contribution of heart rate to this form of syncope, the peripheral circulation plays the dominant role in the induction of neurocardiogenic syncope in most patients. We review in this brief article the physiology of cardiovascular reflexes, which are important for short-term arterial pressure control, and their potential contribution to the pathophysiology of neurocardiogenic syncope. This type of syncope represents a profound failure of the normal mechanisms for short-term regulation of arterial pressure. Any therapeutic strategies for the management of neurocardiogenic syncope must deal with alterations in vascular control, which contribute to its pathogenesis.

A SINGLE DOSE OF RECOMBINANT HUMAN IGF-I (rhIGF-I) DOES NOT AFFECT URINARY EXCRETION OF NITRIC OXIDE METABOLITES IN IDDM. 560

Several studies have shown the potential importance of nitric oxide (NO) in the regulation of peripheral vascular resistance in diabetes. The discovery that IGF-I induces NO production by endothelial cells suggests that IGF-I may be an important regulator of vascular tone in vivo via nitric oxide release from the vascular endothelium and may play a role in control of renal hemodynamics in physiologic and pathologic conditions. We have previously reported that the excretion of NO metabolites(NO2+NO3=NOx) is not significantly different in IDDM compared to controls (n=9; age range 3-17 years). The aim of this study was to evaluate urinary excretion of NOx in response to a single rhIGF-I (n=9; 80 mcg/Kg Sc) or placebo injection (n=9). Urinary excretion of NOx was measured during hospital admission in the 12-hour period preceding and following rhIGF-I or placebo administration in 18 subjects with IDDM without nephropathy (age range 8-16 years, IDDM duration 1-10.5 years, 5 pre-pubertal/13 pubertal). Mean glycosylated hemoglobin was high(11.7±1.9%; nI 4.4-6.1%) while on conventional insulin therapy. Urinary NO3 was reduced to NO2 by E. Coli reductase and total NO2 was analyzed using the Griess reagent. Records were kept by the nurses and accuracy of the collection was validated by creatinine excretion (correlation between creatinine and urinary NO, r=0.51; p<0.01). The data(mean±SD) were analyzed by Student's t-test. A single injection of rhIGF-I did not affect the urinary excretion of NO metabolites. As previously reported, the mean nitric oxide excretion was not significantly different from that observed in controls and did not increase with IDDM duration. Further studies are necessary to evaluate the influence of chronic rhIGF-I administration on nitric oxide metabolism. This study was partially funded by Genentech Inc. and NY State Health Research Council.Table

Angiotensin blockade or calcium antagonists improve endothelial dysfunction in hypertension: studies in perfused mesenteric resistance arteries.

Endothelial regulation of peripheral vascular resistance is impaired in hypertension. We studied the effects of different antihypertensive therapies on endothelial function in perfused mesenteric resistance arteries. Spontaneously hypertensive rats (SHR) aged 7 weeks were treated with either the nonpeptidic angiotensin II (AII) receptor antagonist CGP 48369, the angiotensin-converting enzyme (ACE) inhibitor benazepril HCl, or the calcium antagonist nifedipine (each 10 mg/kg/day orally, p.o.) for 8 weeks. All forms of therapy inhibited the increase in systolic blood pressure (SBP) to a comparable degree (18-23 mm Hg) and reduced but did not normalize medial hypertrophy in SHR. Changes in intraluminal vascular diameter to acetylcholine (ACh), norepinephrine (NE), and endothelin-1 (ET-1) were measured. Impaired endothelium-dependent relaxations to intraluminal ACh improved or normalized with all therapies, whereas the response to extraluminal ACh (which was unimpaired in SHR) remained unaffected. The endothelium-dependent inhibition of contractions to NE was lost in untreated SHR and improved or restored by antihypertensive therapy. In SHR, the sensitivity but not the maximal response of vascular smooth muscle (VSM) to ET-1 was paradoxically decreased. Antihypertensive therapy with CGP 48369, nifedipine, or benazepril HCl restored or increased the sensitivity to ET-1. Thus, chronic blockade of the renin-angiotensin system or voltage-operated calcium channels reduces BP and improves endothelial dysfunction in the resistance circulation of SHR. This may contribute to normalization of peripheral vascular resistance during antihypertensive treatment and improve local blood flow to vital organs.

Spontaneous activity, conduction velocity and segmental origin of different classes of thoracic preganglionic neurons projecting into the cat cervical sympathetic trunk

Previously, in the anesthetized cat, thoracic preganglionic neurons projecting to the superior cervical ganglion were divided into four classes (groups I–IV) by way of their reflex pattern [4, 5]. Neurons of each class are probably involved in a distinct function, such as regulation of peripheral vascular resistance, regulation of blood flow through skin, regulation of pupil diameter, etc. Here it was tested whether the functionally different classes of thoracic preganglionic neurons also differ in the distribution of their segmental origin, their spontaneous activity and the conduction velocity of their axons. The segmental distribution of preganglionic neurons was almost identical to that determined previously with tracer methods. Distinct classes of neurons had different, although overlapping segmental distributions. Most group III neurons were located in segments T1 and T2, whereas group I, II and IV neurons showed a broader distribution. The subpopulations of preganglionic neurons did not differ in their rate of spontaneous activity. No significant difference was found in segmental distribution between neurons with spontaneous activity and silent neurons. No correlation was found between conduction velocity and spontaneous activity. The proportion of unmyelinated units was greater among group I (16.3%), group II (24.1%) and group IV (22.2%) neurons than among group III neurons (8%). The distributions of conduction velocity were significantly different between group I and group III and between group II and group III neurons. Axons of preganglionic neurons located in segments T1 and T2 conducted faster than axons of neurons located more caudally. The present study shows that distinct subpopulations of preganglionic neurons, as defined by their reflex patterns, differ in their segmental location within the spinal cord and with respect to the conduction velocity of their axons.

Endothelium-Dependent Regulation of Resistance Arteries

Small arteries with a diameter of 200 microns or less play an important role in the regulation of peripheral vascular resistance. Dysregulation of vascular tone of these arteries may contribute significantly to high blood pressure. The contractile state of blood vessels is regulated by peripheral neurons, vascular smooth muscle, and the endothelium. In perfused mesenteric resistance arteries of the rat, removal of the endothelium markedly augments the sensitivity and maximal response to norepinephrine and endothelin-1. Acetylcholine causes profound endothelium-dependent relaxation of resistance arteries contracted with norepinephrine or endothelin-1. The potency of the muscarinic agonist is particularly pronounced with intraluminal application. The inhibitory effects of the endothelium against contractions induced by norepinephrine and endothelin-1 are reduced with aging and hypertension. The endothelium-dependent relaxation in response to intraluminal, but not extraluminal, acetylcholine is blunted in mesenteric resistance arteries of hypertensive rats and in the forearm circulation of hypertensive patients studied in vivo. The sensitivity of vascular smooth muscle to the effects of endothelin decreases with advancing age and in the spontaneously hypertensive rat. Thus, endothelium-derived vasoactive substances can profoundly affect vascular tone of resistance arteries studied in vitro and in vivo. The inhibitory effects of the endothelium against vasoconstrictor stimuli decreases with aging and hypertension, indicating a dysfunction of these regulatory mechanisms under these conditions.

Mechanism of the Hypertension Produced by Inhibition of Nitric Oxide Biosynthesis in Rats

Summary: We have examined the effects of inhibition of nitric oxide (NO) biosynthesis on the blood pressure (BP) of anesthetized rats using N-nitro-l-arginine (NOLA). Infusion of NOLA (5, 15, or 60 mg/kg) caused a rise in BP of up to 155 mm Hg that could be prevented (but not reversed) by administration of l-arginine (300 and 600 mg/kg, i.v.). In addition, NOLA (5-60 mg/kg) reduced the duration of the depressor response to acetylcholine (1 μg/kg), but not that of sodium nitroprusside (10 μg/kg). In rats treated with NOLA (15 mg/kg), infusion of the K+ channel antagonist glibenclamide (30 mg/kg) failed to inhibit the residual depressor response to acetylcholine, indicating that this response is not due to hyperpolarization of the vascular smooth muscle via activation of ATP-sensitive K+ channels. NOLA (5 or 15 mg/kg) still produced rises in BP in anesthetized rats treated with the angiotensin-converting enzyme inhibitor enalaprilat (5 mg/kg; rise of 62 ± 6 mm Hg) and in pithed rats infused with norepinephrine (rise of 62 ± 5 mm Hg). These data suggest that NOLA raises arterial pressure by a mechanism that is not dependent on the central nervous system nor on the renin-angiotensin system. Under resting conditions, the continuous production of NO in resistance vessels may play an important role in the regulation of peripheral vascular resistance.

Cardiopulmonary reflex before and after regression of left ventricular hypertrophy in essential hypertension.

Studies that have examined the cardiopulmonary receptor control of circulation in hypertension have produced conflicting results. In 10 normotensive subjects and in age-matched essential hypertensive subjects without (n = 10) or with left ventricular hypertrophy (n = 12), as well as in seven subjects of the latter group restudied after 1 year of treatment that induced regression of cardiac hypertrophy, we examined the cardiopulmonary reflex by increasing central venous pressure and stimulating cardiopulmonary receptors through passive leg raising and by reducing central venous pressure and deactivating cardiopulmonary receptors through nonhypotensive lower body negative pressure. Reflex responses were measured as changes in forearm vascular resistance (mean blood pressure divided by plethysmographically measured blood flow), plasma norepinephrine concentration, and plasma renin activity. In hypertensive subjects without left ventricular hypertrophy, stimulation and deactivation of cardiopulmonary receptors caused changes in forearm vascular resistance, norepinephrine concentration, and plasma renin activity that were modestly reduced as compared with those in normotensive subjects. However, all these changes were markedly reduced in hypertensive subjects with left ventricular hypertrophy. Following regression of left ventricular hypertrophy, the changes in vascular resistance, plasma norepinephrine, and plasma renin activity induced by cardiopulmonary receptor manipulation all improved markedly. These results demonstrate that cardiopulmonary receptor regulation of peripheral vascular resistance and of neurohumoral variables is impaired in essential hypertension and that the impairment is much more pronounced when this condition is associated with cardiac structural alterations. Therapeutic regression of these alterations, however, leads to a marked improvement of this reflex, with consequent favorable effects on circulatory homeostasis.

Hemodynamic changes and renal plasma flow in early heart failure: implications for renin, aldosterone, norepinephrine, atrial natriuretic peptide and prostacyclin.

Vasoconstrictory and vasodilatory hormone systems may be important in the regulation of peripheral vascular resistance and renal hemodynamics in the early phase of heart failure. The activity of the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous activity, and, as possible counterregulating systems, the activity of prostacyclin and atrial natriuretic peptide (ANP) were studied in 6 conscious dogs during the first 4 days of congestive heart failure in relation to hemodynamic changes and renal plasma flow. Congestive heart failure was induced by rapid right ventricular pacing, which caused a considerable decrease of cardiac output (-38%; p less than 0.05), oxygen saturation of the mixed venous blood (-13%; p less than 0.05), and mean arterial pressure (-24 mm Hg; p less than 0.05) on the 4th day. Mean pulmonary arterial pressure and mean pulmonary capillary wedge pressure increased (+4 mm Hg; p less than 0.05 and +7 mm Hg, respectively; p less than 0.05). Renal plasma flow was slightly reduced (N.S.), renal vascular resistance did not change. Peripheral vascular resistance showed a significant increase only on the 1st day. Sympathetic nervous activity was stimulated (from 175 +/- 31 pg/ml to 391 +/- 100 pg/ml; p less than 0.05), while plasma renin concentration was significantly suppressed on the 4th day (from 3.3 +/- 0.4 ngAI/ml/h to 1.9 +/- 0.5 ngAI/ml/h; p less than 0.05), and plasma aldosterone levels were decreased (from 108 +/- 12 pg/ml to 76 +/- 12 pg/ml; p less than 0.05). ANP increased 3-fold (p less than 0.05) and 6-keto-prostaglandin F1 alpha increased in 4 out of 6 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)